We have observed that peripheral blood mononuclear cells (PBMC) from monkeys infected with B. burgdorferi display a downmodulation of the specific T-cell response to heat-killed spirochetes in vitro. PBMC responses to concanavalin A (Con A) were unaltered. To determine the role that cytokines may play in the cellular unresponsiveness, both Th1 (IL-2, IFN-() and Th2 (IL-4 and IL-10) cytokines were investigated in these animals. PBMC from all animals were cultured for 24 hr with media, heat-killed spirochetes, or Con A and cytokine gene expression was assessed by semiquantitative RT-PCR. Cells from all animals showed an elevated level of B. burgdorferi-induced IL-10 with a diminished production of IL-2 mRNA, suggesting a possible role for IL-10 in the T cell unresponsiveness. Neither IL-4 nor IFN-( ( gene expression was ostensibly affected by heat-killed spirochetes. Levels of mRNA for all cytokines in Con A-induced PBMC were increased and not significantly different among animals. Cel l-free supernatants were also collected after 48 hr and ELISA was conducted to determine the production of IL-2, IL-4, IL-10 and IFN-(. As at the mRNA level, heat-killed spirochetes induced significant production of IL-10 but not those of IL-2. IL-4 and IFN-( production was also not detected. Significant production of IL-2, IL-4, IL-10 and IFN-( in Con A-stimulated cultures was seen in all animals. Because of the increase production of IL-10, studies were conducted to determine if neutralization of IL-10 in antigen-stimulated cultures would reverse the antigen-specific unresponsiveness. Addition of human anti-IL-10 neutralizing antibody did not induce significant blastogenesis in response to heat-killed spirochetes. These results show that multiple factors may regulate the antigen-specific cellular unresponsiveness in rhesus monkeys infected with B. burgdorferi. FUNDING CDC, Atlanta, GA PUBLICATIONS None